Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt

Alan J. Bagnall, Nicholas F. Kelland, Fiona Gulliver-Sloan, Anthony P. Davenport, Gillian A. Gray, Masashi Yanagisawa, David J. Webb, Yuri V. Kotelevtsev

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Endothelin B receptors in different tissues regulate diverse physiological responses including vasoconstriction, vasodilatation, clearance of endothelin-1, and renal tubular sodium reabsorption. To examine the role of endothelial cell endothelin B receptors in these processes, we generated endothelial cell-specific endothelin B receptor knockout mice using a Cre-loxP approach. We have demonstrated loss of endothelial cell endothelin B receptor expression and function and preservation of nonendothelial endothelin B receptor-mediated responses through binding and functional assays. Ablation of endothelin B receptors exclusively from endothelial cells produces endothelial dysfunction in the absence of hypertension, with evidence of decreased endogenous release of NO and increased plasma endothelin-1. In contrast to models of total endothelin B receptor ablation, the blood pressure response to a high-salt diet is unchanged in endothelial cell-specific endothelin B receptor knockouts compared with control floxed mice. These findings suggest that the endothelial cell endothelin B receptor mediates a tonic vasodilator effect and that nonendothelial cell endothelin B receptors are important for the regulation of blood pressure.

Original languageEnglish (US)
Pages (from-to)286-293
Number of pages8
JournalHypertension
Volume48
Issue number2
DOIs
StatePublished - Aug 1 2006

Keywords

  • Endothelin
  • Endothelium
  • Mice
  • Receptors, endothelin
  • Vasodilation

ASJC Scopus subject areas

  • Internal Medicine

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    Bagnall, A. J., Kelland, N. F., Gulliver-Sloan, F., Davenport, A. P., Gray, G. A., Yanagisawa, M., Webb, D. J., & Kotelevtsev, Y. V. (2006). Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt. Hypertension, 48(2), 286-293. https://doi.org/10.1161/01.HYP.0000229907.58470.4c